Publication: Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome
5
Issued Date
2020-09-11
Resource Type
ISSN
20453701
Other identifier(s)
2-s2.0-85091381754
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell and Bioscience. Vol.10, No.1 (2020)
Suggested Citation
Ayushi Jain, Phubed Nilatawong, Narinrat Mamak, Laran T. Jensen, Amornrat Naranuntarat Jensen Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome. Cell and Bioscience. Vol.10, No.1 (2020). doi:10.1186/s13578-020-00468-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/58956
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome
Abstract
© 2020 The Author(s). Background: Shwachman-Diamond syndrome (SDS) is a congenital disease that affects the bone marrow, skeletal system, and pancreas. The majority of patients with SDS have mutations in the SBDS gene, involved in ribosome biogenesis as well as other processes. A Saccharomyces cerevisiae model of SDS, lacking Sdo1p the yeast orthologue of SBDS, was utilized to better understand the molecular pathogenesis in the development of this disease. Results: Deletion of SDO1 resulted in a three-fold over-accumulation of intracellular iron. Phenotypes associated with impaired iron-sulfur (ISC) assembly, up-regulation of the high affinity iron uptake pathway, and reduced activities of ISC containing enzymes aconitase and succinate dehydrogenase, were observed in sdo1Δ yeast. In cells lacking Sdo1p, elevated levels of reactive oxygen species (ROS) and protein oxidation were reduced with iron chelation, using a cell impermeable iron chelator. In addition, the low activity of manganese superoxide dismutase (Sod2p) seen in sdo1Δ cells was improved with iron chelation, consistent with the presence of reactive iron from the ISC assembly pathway. In yeast lacking Sdo1p, the mitochondrial voltage-dependent anion channel (VDAC) Por1p is over-expressed and its deletion limits iron accumulation and increases activity of aconitase and succinate dehydrogenase. Conclusions: We propose that oxidative stress from POR1 over-expression, resulting in impaired activity of ISC containing proteins and disruptions in iron homeostasis, may play a role in disease pathogenesis in SDS patients.